lc-ms-detecting-covid-19-blog-322x430Most of the important things in the world have been accomplished by people who have kept on trying when there seemed to be no hope at all.” – Dale Carnegie

The winter sun on 25th December 2020 morning shone brightly. My experience in my 22 years in the USA has been varied. While I could easily stand and grill in someplace warm, some other cities would be colder than a freezer! But, never did I picture myself being masked, gloved, sanitized – before stepping out on Christmas Day. My house, my friends, my neighborhood, my country – have never been this quiet. A virus ranging in size between 70 to 90 nanometers could cause this and change our lives forever.

The number of cases, deaths, and probable cases continue to rise alarmingly. The rules and guidelines from the state change frequently. The PCR tests continue to detect the presence of the COVID-19 virus. But then—there were so many of them who were probably not infected but were found to be positive! Interestingly, there also were many who were infected but not detected. Some positive cases had a low viral load at the time of conducting tests, while some had a different virus, which was mistaken to be COVID-19. Now, if that were to be the only way, the confusion would only add to the miseries. Fortunately, analytical technologies have made advancements that allow us to be a lot more accurate and selective while being sensitive and specific. Liquid Chromatography (LC) coupled to Mass Spectrometry (MS) is one such technology, which can achieve and deliver outstanding confidence in results by capitalizing either the Thermo ScientificTM OrbitrapTM Technology or the Thermo ScientificTM TSQ AltisTM triple-stage quadrupole mass spectrometer (MS). These robust, reliable, reproducible and sensitive LC-MS platforms have been helping a bevy of clinical research laboratories address and achieve their scientific and business goals with ultimate confidence, every day – for years.

It is probably safe to say that it can be extremely complicated for anyone to completely understand a virus, predict its impact, and determine a way to counter the virus before it amplifies enough to gain full control. Hence, the approaches have to be multi-pronged and not necessarily from the same group of researchers. As was found via a quick literature search, the LC-MS based research of COVID-19 primarily adopted three different approaches – i) Understanding proteomic profile in presence of the virus1-3; ii) monitoring therapeutic influence on the viral proteins4; and iii) monitoring critical and targeted viral and/or human plasma proteins to determine and predict the extent of infection5-11.

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For the first approach, the researchers have been monitoring hundreds (nearly a thousand) of proteins within a select group of subjects and published their response based on exposure to the virus. The second approach focuses on determining the efficacy and toxicity of potential drugs and therapeutics that can be used to treat a patient suffering from COVID-19. The third approach, however, enables us to narrow down to a select group of proteins (can also be used as biomarkers) and routinely monitor them. As a subset to the third approach, results are coming out on critical human plasma proteins that can be monitored and quantified routinely. The up-/down-regulation of the plasma proteins can be considered as efficient indicators for the extent of infection caused by the virus and can be used for determining an optimal treatment regime. A good number of clinical research organizations have been using one of these approaches to monitor patient samples every day. It should be noted that each of the above-mentioned approaches can enable the process of development of vaccines. At the time of writing this article, there are several vaccines approved for use across many countries, and several more are in the pipeline showing promise. However, considering the global population, and the chances that such viruses in different shape and form can show up in future, ability to capitalize on such technologies at the right time could turn out to be immensely beneficial.

Life has changed permanently. Directly or indirectly, we all have suffered the onslaught of this virus. A good number of us mourn the loss of a near and dear one. While these changes are irreversible, what we can do is continue the fight. Technologies and their advancements are there to assist, and ultimately will help us deliver the hope we all yearn for.

References

  1. Gouveia, D et al. Shortlisting SARS-CoV-2 peptides for Targeted studies from experimental data-dependent acquisition tandem mass spectrometry data. Proteomics, 2020, 20, 107
  2. Di, B et al. Identification and validation of predictive factors for progression to severe COVID-19 pneumonia by proteomics. Signal Transduction and Targeted Therapy, 2020, 5, 217
  3. Thomas, T et al. Evidence of Structural protein damage and membrane lipid remodeling in Red Blood Cells from COVID-19 patients Journal of Proteome Research, 2020, 19, 4455
  4. Li, Na et al. Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. Journal of Cellular Physiology, 2020, 1-17
  5. Cardozo, KHM et al. Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts. Nature Communications, 2020, 11, 1599
  6. Srivastava, S et al. A multipronged deep omics-based investigation of COVID-19 plasma samples identifies key molecular networks of disease severity progression
  7. Bankar, R, Srivastava, S et al. Proteomic Investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in COVID-19 patients. Cell Reports, 2020, In Progress
  8. Renuse, S et al. Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens MedxRiv, 2020
  9. Bos, R et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. Nature, 2020, 91
  10. Schuster, O et al. Specific and Rapid SARS-CoV-2 Identification Based on LC-MS/MS analysis. MedxRiv, 2020
  11. Chen, Y-M et al. Blood molecular markers associated with COVID‐19 immunopathology and multi‐organ damage. EMBO J, 2020, 0:e105896